The growing appreciation of human genetics and genomics in cardiovascular disease (CVD) accompanied by the technological breakthroughs in genome editing, particularly the CRISPR-Cas9 technologies, has presented an unprecedented opportunity to explore the application of genome editing in cardiovascular medicine. The ever-growing genome editing toolbox includes an assortment of CRISPR-Cas systems with increasing efficiency, precision, flexibility, and targeting capacity. Over the past decade, the advent of large-scale genotyping technologies and genome-wide association studies (GWAS) has provided numerous genotype-phenotype associations for diseases with complex traits. Notably, a growing number of loss-of-function mutations have been associated with favorable CVD risk-factor profiles that may confer protection. Combining the newly gained insights of human genetics with recent breakthrough technologies, such as the CRISPR-Cas9 technologies, holds great promise in elucidating novel disease mechanisms and transforming genes into medicines. Nonetheless, translating genetic insights into novel therapeuties remains challenging. Applications of "in body" genome editing for CVD treatment and engineering cardioprotection remain mostly theoretical. Here we highlight the recent advances of the CRISPR-based genome editing toolbox and discuss the potential and challenges of CRISPR-based technologies for translating GWAS findings into genomic medicines.